Background: We have observed downgrowth of benign gastric glands into gastric neuroendocrine tumors (NET), leading to potential misdiagnosis as composite exocrine-endocrine carcinoma. Entrapment of benign glands in Peutz-Jeghers polyps, colonic adenomas, and pancreatic endocrine tumors is a well-recognized mimic of invasive adenocarcinoma (in polyps) or composite exocrine-endocrine tumors (in the pancreas). However, to our knowledge there has been only one previous report of this phenomenon in the stomach (2 cases reported by Luong TV et al. Virchows Arch. 2008;452:169-74).Design: We studied all available resected gastric NET with at least submucosal invasion from 2002-2012. Cases were jointly reviewed for the following features: NET type (sporadic, MEN1-associated, or autoimmune gastritis [AIG]-associated), presence/depth of epithelial downgrowth, epithelial type (intestinal, fundic, or pyloric), glandular atypia, and mitotic activity of entrapped glands. Lymph node metastases, when present, were also reviewed. Duodenal NET resected during the same period served as controls.Results: There were 54 gastric NET in 29 patients (1-13 tumors/patient). 30 NET arose in AIG, 13 in MEN1, and 11 were sporadic. Epithelial downgrowth occurred in 26 (48%) gastric NET but only 2 of 36 (6%) duodenal NET (p<0.001). Downgrowth was slightly more common in patients with hypergastrinemia (51% vs 36%) but this was not statistically significant. Evidence for the non-neoplastic nature of epithelial downgrowth included: 1) its confinement to submucosa regardless of the depth of NET invasion, and 2) lack of glandular cells in the metastatic lymph nodes of 4 patients with epithelial downgrowth. Specific morphologic features are shown below:

Epithelial Downgrowth

All Gastric NET (n=54)

Sporadic (n=11)

AIG (n=30)

MEN1 (n=13)

Present

26 (48%)

4 (36%)

13 (43%)

9 (69%)

Depth

Submucosa (25, 96%); muscularis mucosae (1, 4%)

Submucosa (4, 100%)

Submucosa (12, 92%); muscularis mucosae (1, 8%)

Submucosa (9, 100%)

Type

Pyloric (22, 85%); intestinal (14, 54%); fundic (7, 27%)

Pyloric (4, 100%); intestinal (2, 50%)

Pyloric (13, 100%); intestinal (9, 69%)

Fundic (7, 78%); pyloric (5, 56%); intestinal (3, 33%)

Mitoses

9 (35%)

1 (25%)

6 (46%)

2 (22%)

Atypia

5 (19%)

1 (25%)

3 (23%)

1 (11%)

Conclusions: Epithelial downgrowth is a common phenomenon, present in almost half of gastric NET but few duodenal NET. Its lack of deep growth and lack of nodal metastases attest to its benign nature. However, reactive atypia and/or mitotic activity within the entrapped glands in some cases raises the potential for misdiagnosis as composite exocrine-endocrine carcinoma.Category: Gastrointestinal